1. The steroid-thyroid hormone receptor superfamily comprises a class of ligand activated transcription factors. Ligand activated members of the superfamily include the receptors for steroids, retinoids, thyroid and vitamin D hormones. There is, however, within this superfamily a group of orphan receptors sharing the structural features of nuclear receptors but lacking ligand specificity. We investigated potential functions of two related orphan receptors Nur 77 and Nurr 1 during rat brain development. We cloned two forms of Nurr 1 from a neonatal mouse brain cDNA library; Nurr 1-long identical to that previously reported and a new form termed Nurr 1-short, generated by alternative splicing. Using specific probes from the most dissimilar amino-terminal regions of Nurr 1 and Nur 77 and Northern blot analyses revealed that Nurr 1 mRNA is detectable not only in embryo and during brain development, but also in adult brain, contrary to the previous report. Nur 77 mRNA was already detectable 8 days after birth and gradually increased to day 18 and then stayed unchanged through the adult life. Our preliminary results using a digoxigenin labeled probe indicate that Nur 77 mRNA are expressed in many regions of adult brain, while Nurr 1 mRNA is more restricted especially to sensory neurons. A long term goal is to target Nurr 1 and Nur 77 genes by homologous recombination technique to determine their physiological roles during rat brain development. 2. We have utilized a differential mRNA display technique to find differences in a subset of mRNA samples prepared from undifferentiated a glial precursor cell line CG4 which differentiate into oligodendrocytes in the absence of mitogens. Several unique messages have been recovered and they are being characterized in a search for genes involved in differentiation.